Do Enzymes Have Built-In Cooling Systems?

The ability to refrigerate the active regions of an enzyme would be hugely advantageous. Now researchers have worked out how this cooling might work.

The study of how molecular machines assemble and maintain our
bodies is one of the defining sciences of our generation. The more we
learn about these machines, the more complex and capable they seem.

One feature common to all machines is that they work best within a
certain temperature range. Many human-built machines have complex
systems for maintaining their temperature.
Similarly, many machines built by evolution have extremely efficient
thermal management systems. Think big ears and sweat glands.

So it seems reasonable to assume that evolution might have found a
way for molecular machines to manage their temperature.

Today, Hans Briegel
at the University of Innsbruck in Austria and Sandu Popescu at the
University of Bristol in the UK, put forward a fascinating suggestion
for how such a thermal management system might work.

The machines they focus on are enzymes, machines which catalyse
certain biochemical reactions.

Essentially, enzymes are molecular
clamps. They grab hold of specific biomolecules and hold them still.
This reduces the activation energy of whatever chemical process the
biomolecules are involved in, thereby increasing the reaction rate.

But the performance of enzymes is extremely sensitive to
temperature. The rate of the reactions they catalyse increases slowly
with temperature until it reaches a maximum and then drops
dramatically.

On a mechanical level, the extra heat increases the amount of
vibration in the molecular structure of the machine. The specific
problem for an enzyme is the vibrations in the set of “molecular
jaws” it uses to grab hold of biomolecules (otherwise called the
activation site).

As the temperature increases, the vibrations in these jaws
increases until they are no longer able to grab the biomolecules they
are designed to hold. That’s when the reaction rate drops
dramatically.

Briegel and Popescu say that it would be hugely advantageous for
an enzyme to be able to cool these jaws. And they map out one way
this could be done, which they call conformational cooling.

The idea is that a small change in the enzyme’s shape stiffens the
jaws temporarily. This has the effect of reducing the vibrations in
the jaws and hence their temperature. When the cooled jaws relax,
they are then able to grab hold of the relevant biomolecules again.
At least until they heat up again.

(The key is that the jaws must relax faster than the rate at which
they heat up, otherwise there’s no advantage.)

Of course, every refrigerator needs a source of power and Briegel
and Popescu suggest that this could be provided by another molecule,
such as ATP.

What’s neat about this suggestion is that a very simple experiment
could easily test it. Simply measure the temperature dependency of
the rate of enzymatic reaction with and without the presence of ATP.

If ATP is really providing the energy to cool the enzyme, then the
two curves should be different.

That’s an experiment that an enterprising grad student could do
tomorrow.